Nephrology drugs i need to know
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I now have enough rich content from the textbooks to write a comprehensive reference guide. Let me compile everything into a well-organized response covering all major nephrology drug classes.
Nephrology Drugs: Complete Reference Guide
Sources: Brenner and Rector's The Kidney; Comprehensive Clinical Nephrology; NKF Primer on Kidney Diseases
1. DIURETICS
Loop Diuretics
Drugs: Furosemide, Bumetanide, Torsemide, Ethacrynic acid
| Feature | Details |
|---|---|
| Site of action | Thick ascending limb of Loop of Henle |
| Mechanism | Block NKCC2 (Na-K-2Cl cotransporter) |
| Efficacy | Most potent diuretics; ceiling effect exists |
| Furosemide PK | 50% oral bioavailability; highly protein-bound; secreted into tubular lumen by OAT1/3; metabolized by UDPGT in liver/gut to inactive glucuronide |
| Clinical uses | Edema (heart failure, cirrhosis, nephrotic), pulmonary edema, hypercalcemia, hyperkalemia |
| Adverse effects | Hypokalemia, hyponatremia, metabolic alkalosis, ototoxicity (high doses, IV), hypomagnesemia, hyperuricemia |
| Drug interaction | NSAIDs blunt natriuresis (inhibit PGE2); probenecid blocks tubular secretion; aminoglycosides increase ototoxicity |
| Resistance | "Braking phenomenon" - homeostatic NaCl retention after initial dose; worsen with low Na+ intake |
SGLT2 inhibitors synergy: Adding an SGLT2 inhibitor to loop diuretics produces a synergistic natriuresis, useful in loop diuretic resistance (especially in diabetic patients).
Thiazide and Thiazide-like Diuretics
Drugs: Hydrochlorothiazide (HCTZ), Chlorthalidone, Indapamide, Metolazone
| Feature | Details |
|---|---|
| Site of action | Early distal convoluted tubule |
| Mechanism | Block NCC (Na-Cl cotransporter) |
| Clinical uses | Hypertension, edema, hypercalciuria, nephrogenic DI |
| Key note | Ineffective in GFR <30 mL/min (except metolazone - still works in CKD) |
| Adverse effects | Hypokalemia, hyponatremia (more than loops), hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia |
| Combination | Metolazone + loop diuretic = synergistic (sequential nephron blockade); powerful combo in refractory edema |
Potassium-Sparing Diuretics
A) Aldosterone Antagonists
- Spironolactone - competitive aldosterone antagonist; blocks ENaC and ROMK in collecting duct; causes gynecomastia, hyperkalemia
- Eplerenone - selective aldosterone antagonist; fewer hormonal side effects; used in heart failure, resistant hypertension
B) ENaC Blockers
- Amiloride, Triamterene - directly block ENaC; useful in hypokalemia, Liddle syndrome; risk of hyperkalemia in CKD
Key use: K-sparing diuretics counteract loop-diuretic-induced K+ loss, especially in volume-depleted states with high aldosterone.
Carbonic Anhydrase Inhibitors
- Acetazolamide - proximal tubule; blocks HCO3- reabsorption; used in metabolic alkalosis, altitude sickness, glaucoma; causes hyperchloremic metabolic acidosis
SGLT2 Inhibitors (Nephroprotective Diuretics)
Drugs: Empagliflozin, Canagliflozin, Dapagliflozin
| Feature | Details |
|---|---|
| Mechanism | Block SGLT2 in proximal tubule → osmotic glucosuria + natriuresis |
| Renal protection | Activate TGF (tubuloglomerular feedback) → reduce glomerular capillary pressure → slow CKD progression |
| Evidence | CREDENCE, DAPA-CKD, EMPA-KIDNEY trials show significant reduction in CKD progression and ESRD |
| Uses | T2DM + CKD, heart failure with CKD, proteinuric CKD |
| Adverse effects | Genital mycotic infections, UTIs, euglycemic DKA (rare), volume depletion |
2. RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS) BLOCKERS
ACE Inhibitors
Drugs: Enalapril, Lisinopril, Ramipril, Captopril, Benazepril
| Feature | Details |
|---|---|
| Mechanism | Inhibit ACE → reduce Ang II → efferent arteriolar dilation → reduce intraglomerular pressure |
| Main renal use | Reduce proteinuria, slow CKD progression (esp. diabetic nephropathy) |
| Potentiate diuretics | ACE inhibitors enhance furosemide natriuresis by suppressing aldosterone |
| Adverse effects | Hyperkalemia, acute rise in creatinine (up to 30% acceptable), cough (bradykinin), angioedema |
| Contraindications | Bilateral RAS, single kidney with RAS, pregnancy, severe hyperkalemia |
ARBs (Angiotensin Receptor Blockers)
Drugs: Losartan, Irbesartan, Valsartan, Candesartan, Olmesartan
- Same renal indications as ACEi; preferred if ACEi cough
- Losartan has uricosuric property (useful in gout with hypertension)
- No combination of ACEi + ARB - increased harm without added renal benefit (ONTARGET trial)
Direct Renin Inhibitors
- Aliskiren - rarely used; contraindicated with ACEi/ARB in diabetics
MRA (Mineralocorticoid Receptor Antagonists)
- Finerenone - non-steroidal MRA; FIDELIO-DKD/FIGARO-DKD trials show CV and renal protection in T2DM with CKD; lower hyperkalemia risk vs spironolactone
3. IMMUNOSUPPRESSANTS (Transplant Nephrology)
Calcineurin Inhibitors (CNIs) - Backbone of Transplant Immunosuppression
Mechanism: Inhibit calcineurin (Ca2+-dependent phosphatase) → prevent NFAT dephosphorylation → block IL-2 transcription → suppress T-cell proliferation
| Drug | Binding Protein | Key Points |
|---|---|---|
| Cyclosporine | Cyclophilin | Microemulsion form (Neoral) preferred; monitor 12h trough or C2 level; side effects: HTN, hyperlipidemia, gingival hyperplasia, hypertrichosis |
| Tacrolimus | FKBP-12 | 10-100x more potent than CsA; preferred in most centers; side effects: neurotoxicity, NODAT (new-onset diabetes), alopecia, less cosmetic issues than CsA |
CNI nephrotoxicity: Both cause afferent arteriolar vasoconstriction → acute or chronic nephrotoxicity; contributes to long-term allograft loss.
mTOR Inhibitors (Proliferation Signal Inhibitors)
| Drug | Binding Protein | Mechanism |
|---|---|---|
| Sirolimus (Rapamycin) | FKBP-12 | Binds mTORC1 → blocks T-cell and B-cell proliferation |
| Everolimus | FKBP-12 | Similar; shorter half-life |
Uses: CNI-sparing protocols, post-transplant malignancy (antiproliferative), BK nephropathy
Side effects: Impaired wound healing, hyperlipidemia, thrombocytopenia, pneumonitis, mouth ulcers, proteinuria, poor wound healing (avoid in immediate post-op)
Antiproliferative Agents
| Drug | Mechanism | Use |
|---|---|---|
| Mycophenolate mofetil (MMF) | Inhibits IMPDH → blocks de novo purine synthesis → selective suppression of T & B cells | Maintenance immunosuppression (with CNI + steroid); reduces rejection and CNI doses |
| Mycophenolate sodium (EC-MPS) | Same; enteric-coated formulation | Less GI side effects |
| Azathioprine | Purine analogue; inhibits DNA synthesis | Older agent; still used where MMF unavailable; risk: bone marrow suppression; interaction with allopurinol (DANGEROUS - dose reduction needed) |
Corticosteroids
- Prednisolone/Methylprednisolone - cornerstone of induction and maintenance; anti-inflammatory; used in rejection episodes (IV methylprednisolone pulse)
- Side effects: NODAT, osteoporosis, Cushingoid features, hypertension, avascular necrosis, infections
- Many centers pursue steroid minimization/withdrawal protocols
Biologic Induction Agents
| Drug | Type | Mechanism | Use |
|---|---|---|---|
| Basiliximab | IL-2R antagonist (monoclonal Ab) | Blocks CD25 (IL-2 receptor) on T-cells | Standard induction in most transplants |
| Anti-thymocyte globulin (ATG) - rabbit (Thymoglobulin) | Polyclonal Ab | Depletes T-cells | High-immunological-risk recipients, rejection treatment |
| Alemtuzumab (Campath) | Anti-CD52 mAb | Depletes T and B cells | Some induction protocols |
| Rituximab | Anti-CD20 mAb | Depletes B cells | ABMR, desensitization, ABO-incompatible transplant |
| IVIg | Pooled human Ig | Neutralizes anti-HLA Ab, inhibits complement, modulates B cells | Desensitization, ABMR treatment, DSA reduction |
Eculizumab
- Anti-C5 complement inhibitor; used in atypical HUS (aHUS) and recurrent complement-mediated diseases post-transplant
- Requires meningococcal vaccination before use
4. ERYTHROPOIESIS-STIMULATING AGENTS (ESAs)
Used for anemia of CKD (reduced endogenous EPO from diseased kidneys).
| Drug | Notes |
|---|---|
| Epoetin alfa/beta | Short-acting; 2-3x/week dosing; SC preferred in pre-dialysis; IV in HD |
| Darbepoetin alfa | Hyperglycosylated EPO analogue; longer half-life; weekly or q2w dosing |
| Methoxy PEG-epoetin beta (CERA) | Continuous EPO receptor activator; monthly dosing |
Target Hgb: 10-11.5 g/dL (avoid >13 g/dL - increased CV/stroke risk per TREAT trial)
ESA hyporesponsiveness causes: Iron deficiency (most common), infection/inflammation, hyperparathyroidism, aluminum toxicity, pure red cell aplasia (PRCA - rare anti-EPO antibodies)
HIF-PHI (Hypoxia-Inducible Factor - Prolyl Hydroxylase Inhibitors) - Newer class:
- Roxadustat, Daprodustat, Vadadustat - oral agents; stabilize HIF → stimulate endogenous EPO; approved in some countries; oral advantage in pre-dialysis CKD
5. PHOSPHATE BINDERS (Hyperphosphatemia in CKD/ESRD)
| Drug | Type | Key Points |
|---|---|---|
| Calcium carbonate | Ca-based | Cheap; risk of hypercalcemia, vascular calcification; take with meals |
| Calcium acetate | Ca-based | More effective than carbonate; less Ca2+ absorption |
| Sevelamer carbonate/HCl | Non-Ca, non-Al | Also lowers LDL; no calcium load; GI side effects |
| Lanthanum carbonate | Non-Ca | Chewable; effective; lanthanum accumulation (theoretical concern) |
| Sucroferric oxyhydroxide | Iron-based | Low systemic iron absorption; GI side effects |
| Ferric citrate | Iron-based | Also treats iron deficiency; raises serum iron |
| Aluminum hydroxide | Al-based | Highly effective; only short-term use; risk of aluminum toxicity (dementia, bone disease) |
6. VITAMIN D AND MINERAL METABOLISM
| Drug | Type | Use |
|---|---|---|
| Calcitriol (1,25-OH2 vit D) | Active vitamin D | Secondary hyperparathyroidism in CKD; suppresses PTH |
| Alfacalcidol | 1-alpha-OH vit D | Converted to calcitriol in liver; used in CKD |
| Paricalcitol | Selective vitamin D receptor activator | Less hypercalcemia/hyperphosphatemia than calcitriol; preferred in dialysis pts |
| Doxercalciferol | Vitamin D2 analogue | Similar to paricalcitol |
| Cinacalcet | Calcimimetic | Activates Ca-sensing receptor on parathyroid → lowers PTH, Ca, Phos; used in secondary/tertiary hyperparathyroidism; nausea/vomiting common |
| Etelcalcetide | IV calcimimetic | IV formulation; given 3x/week with HD; better compliance than oral cinacalcet |
7. DRUGS FOR HYPERKALEMIA
| Drug | Mechanism | Notes |
|---|---|---|
| Calcium gluconate/chloride | Membrane stabilization | Acute/emergency; does NOT lower K+ |
| Insulin + Dextrose | Shifts K+ into cells | Onset 15-30 min; lasts 4-6 hours |
| Salbutamol (nebulized) | Beta-2 agonist; K+ shift | Additional 0.5-1 mEq/L reduction |
| Sodium bicarbonate | K+ shift (metabolic alkalosis) | Mainly useful if concurrent acidosis |
| Sodium polystyrene sulfonate (Kayexalate) | Cation exchange resin | Slow onset; GI side effects; sorbitol risk of colonic necrosis |
| Patiromer | Potassium binder | Better tolerated; used for chronic hyperkalemia in CKD/HF on RAAS therapy |
| Sodium zirconium cyclosilicate (SZC) | Potassium binder | Fast onset (1h); used acutely and chronically; well tolerated |
| Dialysis | Direct K+ removal | Definitive for severe/refractory hyperkalemia |
8. DRUGS FOR METABOLIC ACIDOSIS IN CKD
- Sodium bicarbonate (oral) - first-line; slows CKD progression; target serum HCO3- >22 mEq/L
- Sodium citrate/citric acid (Shohl's solution) - alternative; avoid in aluminum-containing antacid users
- Veverimer - non-absorbed oral acid binder; removes HCl from GI tract; in trials for CKD acidosis
9. DRUG DOSING IN CKD - KEY PRINCIPLES
| Category | Key Adjustments |
|---|---|
| Renally cleared drugs | Reduce dose or increase interval (aminoglycosides, vancomycin, digoxin, metformin, LMWH) |
| Nephrotoxic drugs to avoid/monitor | NSAIDs, aminoglycosides, contrast agents, amphotericin B, acyclovir (at high doses) |
| Drugs accumulating in ESRD | Gabapentin, morphine metabolites (M6G), metformin (lactic acidosis - hold if eGFR <30) |
| Drug-induced AKI | Contrast nephropathy (use iso-osmolar contrast + hydration), NSAIDs, ACEi in RAS |
10. QUICK DRUG-DISEASE PAIRINGS
| Condition | First-line Drug(s) |
|---|---|
| Diabetic nephropathy (T2DM) | ACEi/ARB + SGLT2i + Finerenone |
| IgA Nephropathy | Sparsentan (dual AT1/endothelin blocker - newer); SGLT2i; ACEi/ARB |
| Focal Segmental Glomerulosclerosis | Steroids, CNIs, MMF |
| Membranous Nephropathy | Rituximab (now preferred over CNI); cyclophosphamide + steroids (Ponticelli) |
| ANCA Vasculitis | Rituximab or Cyclophosphamide + high-dose steroids (induction); Avacopan (C5aR inhibitor) |
| Lupus Nephritis | Hydroxychloroquine + MMF + steroids; Belimumab, Voclosporin (newer) |
| Minimal Change Disease | Steroids (high remission rate); CNI or rituximab for refractory |
| aHUS | Eculizumab (anti-C5); Ravulizumab (longer-acting) |
| Secondary hyperparathyroidism | Cinacalcet or Paricalcitol + Phosphate binder |
| Anemia of CKD | Iron + ESA; HIF-PHI (oral alternative) |
Sources:
- Brenner and Rector's The Kidney, 2-Volume Set (pp. 2261-2337 on diuretics; pp. 2969-3053 on transplant immunosuppression; pp. 2739+ on ESAs)
- Comprehensive Clinical Nephrology, 7th Edition
- NKF Primer on Kidney Diseases, 8th Edition
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